Immunocytochemical localization of neurotransmitters at the light and EM level was used to determine the potential functional role of the neurotransmitter in the neural circuitry of the medullary and spinal dorsal horn. Serotonin, a monoamine neurotransmitter was shown to modulate the transmission of nociceptive information through synapses on thalamic projection neurons in both laminae I and V of the monkey. This observation demonstrates that serotonin acts on postsynaptic receptors, located on thalamic projection neurons. Vasoactive intestinal polypeptide was localized to unmyelinated primary afferent axons in the superficial layers of the sacral spinal cord of the monkey. VIP may represent a neurotransmitter in a discrete class of unmyelinated nociceptors which are confined to a unique class of afferents at sacral levels.